1-196601576-A-G

Variant names:

• chr1-196601576-A-G
• rs10754196
• NM_198503.5:c.95+6639T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198503.5(KCNT2):​c.95+6639T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,020 control chromosomes in the GnomAD database, including 7,028 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7028 hom., cov: 32)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

Genes affected

KCNT2 (HGNC:18866): (potassium sodium-activated channel subfamily T member 2) Enables chloride-activated potassium channel activity. Involved in potassium ion export across plasma membrane. Located in plasma membrane. Implicated in developmental and epileptic encephalopathy 57. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.95+6639T>C		intron_variant	Intron 1 of 27	ENST00000294725.14	NP_940905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14	c.95+6639T>C		intron_variant	Intron 1 of 27	1	NM_198503.5	ENSP00000294725.8

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45487 AN: 151904 Hom.: 7021 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.308

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.299 AC: 45521 AN: 152020 Hom.: 7028 Cov.: 32 AF XY: 0.304 AC XY: 22627 AN XY: 74330

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.306

Alfa AF: 0.297 Hom.: 3391

Bravo AF: 0.301

Asia WGS AF: 0.340 AC: 1180 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10754196; hg19: chr1-196570706;